Antibodies that bind with high specificity and affinity to almost any structural epitope are routinely used as research tools and as FDA approved therapeutics. As a result, therapeutic and diagnostic monoclonal antibodies constitute a multi-billion dollar market worldwide.
Classical methods of immunizing animals to obtain antibodies are slow and cumbersome. As a consequence, several methods have been developed for ex vivo selection of an antibody to a desired target molecule using synthetic antibody libraries. In some methods, libraries of antibodies, or fragments thereof, are displayed on the surface of an organism (for example, a yeast cell, bacterial cell or mammalian cell) or a sub-microscopic agent (for example, a bacteriophage or virus), and the organism or sub-microscopic agent is selected for expression of the desired antibody. In other methods, antibody libraries are expressed and selected in a cell free in vitro system. Current in vitro expression systems, although good at expressing single antibody variable domains, are inefficient at expressing multi-domain antibodies such as single chain antibody (scFv) molecules. This is due to both the structure of current scFv antibody libraries and to the reaction conditions of the current in vitro expression systems.
There is, therefore, a need in the art for improved antibody libraries for selection of scFv antibodies against a desired target.